Classic Congenital Adrenal Hyperplasia

Narrative Review Assesses Current Treatment Challenges and the Evolving Classic Congenital Adrenal Hyperplasia (CAH) Therapeutic Landscape Non-Glucocorticoid (GC) Mechanisms for Treatment of CAH Could Enable Control of Excess ACTH and Androgens Without the Need for High-Dose GCs, Reducing Related Complications Over a Lifetime SAN DIEGO, Jan. 8, 2025 /PRNewswire/ -- Neurocrine Biosciences, Inc. (Nasdaq: NBIX) today announced publication of a narrative review discussing the challenges of traditional treatment of classic congenital adrenal hyperplasia (CAH) with glucocorticoids (GCs) alone and the potential benefits of introducing novel non-GC mechanisms for treating the condition that may enable lower, more physiologic GC dosing. The publication appears in Expert Review of Endocrinology & Metabolism. Treatment of classic CAH is a lifelong challenge that involves balancing the need to manage excess adrenocorticotropic hormone (ACTH) and androgens — historically achieved through high doses of GCs — while managing the risks associated with GC-related complications. The review, Glucocorticoid Therapy in Classic Congenital Adrenal Hyperplasia: Traditional and New Treatment Paradigms, provides information for healthcare providers as they navigate the evolving classic CAH therapeutic landscape. "The treatment paradigm for CAH involves continually monitoring and balancing ACTH and androgen levels and glucocorticoid-dosing to optimize treatment," said Irina Bancos, M.S., M.D., Professor of Medicine, Division of Endocrinology at the Mayo Clinic. "New CAH medications that control excess ACTH and adrenal androgens through a non-glucocorticoid mechanism allow for glucocorticoid dose reduction, with the cumulative reduction over time translating into a significant decrease in the risk for complications that can occur when higher doses are used over a patient's lifetime." "Chronic exposure to high-dose glucocorticoid treatment can result in severe cardiovascular, metabolic and skeletal complications, as well as negatively impact the mental health and quality of life of patients," said Eiry W. Roberts, M.D., Chief Medical Officer, Neurocrine Biosciences. "Over a lifetime, even modest reductions in daily glucocorticoid doses can reduce the risk of these complications and lessen the overall burden of glucocorticoid exposure." CAH presents a significant challenge for individuals living with the condition, their families and the healthcare providers who treat them. The condition leads to excess androgen production and has traditionally required high-dose GC treatment, both of which can have serious consequences. Until recently, treatment options have been limited, highlighting the unmet need for innovative new therapies for CAH. The FDA recently approved CRENESSITY™ (crinecerfont) as an adjunctive treatment to GC replacement to control androgens in adult and pediatric patients four years of age and older with classic CAH. CRENESSITY, a potent and selective oral corticotropin-releasing factor type 1 receptor (CRF1) antagonist, is the first and only classic CAH treatment that directly reduces excess ACTH and downstream adrenal androgen production, allowing for GC dose reduction. About Congenital Adrenal Hyperplasia Congenital adrenal hyperplasia (CAH) is a rare genetic condition that results in an enzyme deficiency that alters the production of adrenal steroid hormones, such as cortisol, aldosterone and adrenal androgens, which are essential for life. Approximately 95% of CAH cases are caused by variants of the CYP21A2 gene that leads to deficiency of the enzyme 21-hydroxylase (21-OH). Severe deficiency of this enzyme leads to an inability of the adrenal glands to produce enough cortisol and, in approximately 75% of cases, aldosterone. Because individuals with CAH are still able to produce androgens, the unused precursors that would normally be used to make cortisol instead result in the production of excess amounts of androgens. If left untreated, CAH can result in salt wasting, dehydration and even death. Historically, exogenous glucocorticoids (GCs) have been used not only to correct the endogenous cortisol deficiency, but doses used are higher than cortisol replacement needed (supraphysiologic) to lower the levels of adrenocorticotropic hormone (ACTH) and adrenal androgens. However, GC treatment at high doses has been associated with serious and significant complications of steroid excess, including metabolic issues such as weight gain and diabetes, cardiovascular disease and osteoporosis. Additionally, long-term treatment with high-dose GCs may have psychological and cognitive impact, such as changes in mood and memory. Adrenal androgen excess has been associated with abnormal bone growth and development in pediatric patients, female health problems such as excess facial hair growth and menstrual irregularities, testicular rest tumors in males and fertility issues in both sexes. About CRENESSITY™ (crinecerfont) CRENESSITY™ is a potent and selective, oral corticotropin-releasing factor type 1 receptor (CRF1) antagonist developed to reduce and control excess adrenocorticotropic hormone (ACTH) and adrenal androgens through a non-glucocorticoid (GC) mechanism for the treatment of classic congenital adrenal hyperplasia (CAH). Antagonism of CRF1 receptors in the pituitary has been shown to decrease ACTH levels, which in turn decreases the production of adrenal androgens and potentially the symptoms associated with CAH. The robust clinical study data demonstrate that lowering adrenal androgen levels with CRENESSITY enables lower, more physiologic dosing of GCs to replace missing cortisol. CRENESSITY comes in capsules and an oral solution. The capsule formulation is available in 50 mg and 100 mg doses. The oral solution is available as a 50 mg/mL strength formulation. For adults 18 years and older, the recommended dosage is 100 mg twice daily taken orally with a meal. For pediatric patients four to 17 years of age weighing less than 55 kg (121 lbs), the recommended dosage is based on body weight and is administered twice daily, taken orally with a meal. For pediatric patients weighing more than 55 kg (121 lbs), the recommended dosage is 100 mg twice daily taken orally with a meal. Healthcare providers can work with patients to determine the appropriate formulation for use depending on patient needs. Patients receiving CRENESSITY should continue GC therapy for cortisol replacement. Important Information Approved Uses CRENESSITY (crinecerfont) is a prescription medicine used together with glucocorticoids (steroids) to control androgen (testosterone-like hormone) levels in adults and children 4 years of age and older with classic congenital adrenal hyperplasia (CAH). IMPORTANT SAFETY INFORMATION Do not take CRENESSITY if you: Are allergic to crinecerfont, or any of the ingredients in CRENESSITY. CRENESSITY may cause serious side effects, including: Allergic Reactions. Symptoms of an allergic reaction include tightness of the throat, trouble breathing or swallowing, swelling of the lips, tongue, or face, and rash. If you have an allergic reaction to CRENESSITY, get emergency medical help right away and stop taking CRENESSITY. Risk of Sudden Adrenal Insufficiency or Adrenal Crisis With Too Little Glucocorticoid (Steroid) Medicine. Sudden adrenal insufficiency or adrenal crisis can happen in people with congenital adrenal hyperplasia who are not taking enough glucocorticoid (steroid) medicine. You should continue taking your glucocorticoid (steroid) medicine during treatment with CRENESSITY. Certain conditions such as infection, severe injury, or shock may increase your risk for sudden adrenal insufficiency or adrenal crisis. Tell your healthcare provider if you get a severe injury, infection, illness, or have planned surgery during treatment. Your healthcare provider may need to change your dose of glucocorticoid (steroid) medicine. Before taking CRENESSITY, tell your healthcare provider about all of your medical conditions, including if you are pregnant or plan to become pregnant, or are breastfeeding or plan to breastfeed. Tell your healthcare provider about all the medicines you take, including prescription and over-the- counter medicines, vitamins, and herbal supplements. The most common side effects of CRENESSITY in adults include tiredness, headache, dizziness, joint pain, back pain, decreased appetite, and muscle pain. The most common side effects of CRENESSITY in children include headache, stomach pain, tiredness, nasal congestion, and nose bleeds. These are not all the possible side effects of CRENESSITY. Call your healthcare provider for medical advice about side effects. You are encouraged to report negative side effects of prescription drugs to the FDA. Visit MedWatch at www.fda.gov/medwatch or call 1-800-FDA-1088. Dosage Forms and Strengths: CRENESSITY is available in 50 mg and 100 mg capsules and as an oral solution of 50 mg/mL. Please see full Prescribing Information About Neurocrine Biosciences, Inc. Neurocrine Biosciences is a leading neuroscience-focused, biopharmaceutical company with a simple purpose: to relieve suffering for people with great needs. We are dedicated to discovering and developing life-changing treatments for patients with under-addressed neurological, neuroendocrine and neuropsychiatric disorders. The company's diverse portfolio includes FDA-approved treatments for tardive dyskinesia, chorea associated with Huntington's disease, classic congenital adrenal hyperplasia, endometriosis* and uterine fibroids,* as well as a robust pipeline including multiple compounds in mid- to late-phase clinical development across our core therapeutic areas. For three decades, we have applied our unique insight into neuroscience and the interconnections between brain and body systems to treat complex conditions. We relentlessly pursue medicines to ease the burden of debilitating diseases and disorders, because you deserve brave science. For more information, visit neurocrine.com, and follow the company on LinkedIn, X (formerly Twitter) and Facebook. (*in collaboration with AbbVie) The NEUROCRINE BIOSCIENCES Logo Lockup and YOU DESERVE BRAVE SCIENCE are registered trademarks of Neurocrine Biosciences, Inc. CRENESSITY and CAHtalyst are trademarks of Neurocrine Biosciences, Inc. Forward-Looking Statements In addition to historical facts, this press release contains forward-looking statements that involve a number of risks and uncertainties. These statements include, but are not limited to, statements regarding the potential benefits to be derived from CRENESSITY for the treatment of classic congenital adrenal hyperplasia (CAH); the value and benefits CRENESSITY brings to patients with CAH; the ability of Neurocrine Biosciences to ensure patients have access to CRENESSITY; and whether the results from our clinical trials of CRENESSITY are indicative of real-world results. Factors that could cause actual results to differ materially from those stated or implied in the forward-looking statements include, but are not limited to, the following: risks and uncertainties associated with Neurocrine Biosciences' business and finances in general, as well as risks and uncertainties associated with the commercialization of CRENESSITY; whether CRENESSITY receives adequate reimbursement from third-party payors; the degree and pace of market uptake of CRENESSITY; risks and uncertainties relating to competitive products and technological changes that may limit demand for CRENESSITY; risks associated with the Company's dependence on third parties for development and manufacturing activities related to CRENESSITY, and the ability of the Company to manage these third parties; risks that additional regulatory submissions for CRENESSITY or other product candidates may not occur or be submitted in a timely manner; risks that the FDA or other regulatory authorities may make adverse decisions regarding CRENESSITY; risks that post-approval CRENESSITY commitments or requirements may be delayed; risks that CRENESSITY may be precluded from commercialization by the proprietary or regulatory rights of third parties, or have unintended side effects, adverse reactions or incidents of misuse; risks and uncertainties relating to competitive products and technological changes that may limit demand for CRENESSITY; and other risks described in the Company's periodic reports filed with the Securities and Exchange Commission, including without limitation the Company's quarterly report on Form 10-Q for the quarter ended September 30, 2024. Neurocrine Biosciences disclaims any obligation to update the statements contained in this press release after the date hereof other than required by law. © 2025 Neurocrine Biosciences, Inc. All Rights Reserved. CAP-CFT-US-0016 01/2025 View original content to download multimedia:https://www.prnewswire.com/news-releases/neurocrine-biosciences-announces-publication-on-traditional-glucocorticoid-treatment-in-classic-congenital-adrenal-hyperplasia-in-expert-review-of-endocrinology--metabolism-302345127.html SOURCE Neurocrine Biosciences, Inc. Neurocrine Biosciences, Inc., Media: Aimee White, 1-858-354-7865, media@neurocrine.com. Investors: Todd Tushla, 1-858-617-7143, ir@neurocrine.com

CRENESSITY, a First-in-Class Treatment for Classic Congenital Adrenal Hyperplasia (CAH), is now commercially available in the U.S. CAH-trained pharmacists are available 24/7 to support patients with prescriptions exclusively through PANTHERx Rare, a specialty pharmacy Neurocrine Access Support is available to provide free, comprehensive access and support information to patients, caregivers and healthcare providers SAN DIEGO, Dec. 20, 2024 /PRNewswire/ -- Neurocrine Biosciences, Inc. (Nasdaq: NBIX) today announced CRENESSITY™ (crinecerfont) is now commercially available in the United States. CRENESSITY was recently approved by the U.S. Food and Drug Administration as an adjunctive treatment to glucocorticoid replacement to control androgens in adult and pediatric patients four years of age and older with classic congenital adrenal hyperplasia (CAH). CRENESSITY, a potent and selective oral corticotropin-releasing factor type 1 receptor (CRF1) antagonist, is a first-in-class therapy for classic CAH that directly reduces adrenocorticotropic hormone and downstream adrenal androgen production. It is the first and only classic CAH treatment that allows people to take lower doses of glucocorticoids while maintaining or improving their androgen levels. "Individuals with CAH and their families have faced ongoing challenges with managing the condition with high-dose steroids alone for the past 70 years," said Kyle W. Gano, Ph.D., Chief Executive Officer, Neurocrine Biosciences. "We're proud to now provide CRENESSITY to the community, and we are committed to supporting patients in obtaining treatment with CRENESSITY through our comprehensive assistance program." CRENESSITY is exclusively available through PANTHERx Rare, a specialty pharmacy, to centralize and simplify CRENESSITY prescriptions. PANTHERx Rare has CAH-trained pharmacists available 24/7 to patients, caregivers and healthcare providers to answer questions and address concerns. Neurocrine Biosciences is committed to supporting patients in obtaining treatment with CRENESSITY by offering Neurocrine Access Support, a free, comprehensive assistance program created for patients, caregivers and healthcare providers. It offers a range of options specifically designed to ensure patients with CAH have everything they need to begin and continue taking CRENESSITY. A dedicated Care Coordinator, backed by a team, is available to help patients and caregivers navigate the insurance process and identify appropriate financial assistance options. The company expects 90% of patients will have a monthly copay of $12 or less. For more information, visit or call 1-855-CRNSITY (276-7489) Monday-Friday 8 am-8 pm ET. The U.S. Food and Drug Administration approval of CRENESSITY was supported by the largest-ever clinical trial program of classic CAH, the CAHtalyst™ Pediatric study, conducted in ages four to 17, and the CAHtalyst Adult study. View the press release announcing the initial FDA approval of CRENESSITY here. For more information about CRENESSITY, visit Crenessity.com. About Congenital Adrenal Hyperplasia Congenital adrenal hyperplasia (CAH) is a rare genetic condition that results in an enzyme deficiency that alters the production of adrenal steroid hormones, such as cortisol, aldosterone and adrenal androgens, which are essential for life. Approximately 95% of CAH cases are caused by variants of the CYP21A2 gene that leads to deficiency of the enzyme 21-hydroxylase (21-OH). Severe deficiency of this enzyme leads to an inability of the adrenal glands to produce enough cortisol and, in approximately 75% of cases, aldosterone. Because individuals with CAH are still able to produce androgens, the unused precursors that would normally be used to make cortisol instead result in the production of excess amounts of androgens. If left untreated, CAH can result in salt wasting, dehydration and even death. Historically, exogenous glucocorticoids (GCs) have been used not only to correct the endogenous cortisol deficiency, but doses used are higher than cortisol replacement needed (supraphysiologic) to lower the levels of adrenocorticotropic hormone (ACTH) and adrenal androgens. However, GC treatment at high doses has been associated with serious and significant complications of steroid excess, including metabolic issues such as weight gain and diabetes, cardiovascular disease and osteoporosis. Additionally, long-term treatment with high-dose GCs may have psychological and cognitive impact, such as changes in mood and memory. Adrenal androgen excess has been associated with abnormal bone growth and development in pediatric patients, female health problems such as excess facial hair growth and menstrual irregularities, testicular rest tumors in males and fertility issues in both sexes. About The CAHtalyst™ Studies The Phase 3 CAHtalyst™ global registrational studies were designed to evaluate the safety, efficacy and tolerability of CRENESSITY in children and adults with classic congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency. The CAHtalyst studies were the largest-ever clinical trial program in classic CAH, including 285 pediatric and adult patients. The CAHtalyst Pediatric study included 103 pediatric patients aged four to 17 years. The study tested two questions. The first question evaluated whether four weeks of CRENESSITY treatment could improve androgen control. The second question evaluated whether an additional 24 weeks of CRENESSITY treatment enabled customized glucocorticoid (GC) down-titration while androstenedione levels were maintained or improved. The CAHtalyst Adult study included 182 adult patients aged 18 to 58 years. Similarly, the first question of the study evaluated whether four weeks of CRENESSITY treatment could improve androgen control, and the second question evaluated whether an additional 20 weeks of CRENESSITY treatment enabled GC reduction to physiologic range while androstenedione levels were maintained or improved. Data from the CAHtalyst Phase 3 studies supported approval of CRENESSITY by the U.S. Food and Drug Administration in December 2024. The open-label extension treatment portions of both studies are ongoing. About CRENESSITY™ (crinecerfont) CRENESSITY™ is a potent and selective, oral corticotropin-releasing factor type 1 receptor (CRF1) antagonist developed to reduce and control excess adrenocorticotropic hormone (ACTH) and adrenal androgens through a non-glucocorticoid (GC) mechanism for the treatment of classic congenital adrenal hyperplasia (CAH). Antagonism of CRF1 receptors in the pituitary has been shown to decrease ACTH levels, which in turn decreases the production of adrenal androgens and potentially the symptoms associated with CAH. The robust clinical study data demonstrate that lowering adrenal androgen levels with CRENESSITY enables lower, more physiologic dosing of GCs to replace missing cortisol. CRENESSITY comes in capsules and an oral solution. The capsule formulation is available in 50 mg and 100 mg doses. The oral solution is available as a 50 mg/mL strength formulation. For adults 18 years and older, the recommended dosage is 100 mg twice daily taken orally with a meal. For pediatric patients four to 17 years of age weighing less than 55 kg (121 lbs), the recommended dosage is based on body weight and is administered twice daily, taken orally with a meal. For pediatric patients weighing more than 55 kg (121 lbs), the recommended dosage is 100 mg twice daily taken orally with a meal. Healthcare providers can work with patients to determine the appropriate formulation for use depending on patient needs. Patients receiving CRENESSITY should continue GC therapy for cortisol replacement. Important Information Approved Uses CRENESSITY (crinecerfont) is a prescription medicine used together with glucocorticoids (steroids) to control androgen (testosterone-like hormone) levels in adults and children 4 years of age and older with classic congenital adrenal hyperplasia (CAH). IMPORTANT SAFETY INFORMATION Do not take CRENESSITY if you: Are allergic to crinecerfont, or any of the ingredients in CRENESSITY. CRENESSITY may cause serious side effects, including: Allergic Reactions. Symptoms of an allergic reaction include tightness of the throat, trouble breathing or swallowing, swelling of the lips, tongue, or face, and rash. If you have an allergic reaction to CRENESSITY, get emergency medical help right away and stop taking CRENESSITY. Risk of Sudden Adrenal Insufficiency or Adrenal Crisis With Too Little Glucocorticoid (Steroid) Medicine. Sudden adrenal insufficiency or adrenal crisis can happen in people with congenital adrenal hyperplasia who are not taking enough glucocorticoid (steroid) medicine. You should continue taking your glucocorticoid (steroid) medicine during treatment with CRENESSITY. Certain conditions such as infection, severe injury, or shock may increase your risk for sudden adrenal insufficiency or adrenal crisis. Tell your healthcare provider if you get a severe injury, infection, illness, or have planned surgery during treatment. Your healthcare provider may need to change your dose of glucocorticoid (steroid) medicine. Before taking CRENESSITY, tell your healthcare provider about all of your medical conditions, including if you are pregnant or plan to become pregnant, or are breastfeeding or plan to breastfeed. Tell your healthcare provider about all the medicines you take, including prescription and over-the counter medicines, vitamins, and herbal supplements. The most common side effects of CRENESSITY in adults include tiredness, headache, dizziness, joint pain, back pain, decreased appetite, and muscle pain. The most common side effects of CRENESSITY in children include headache, stomach pain, tiredness, nasal congestion, and nose bleeds. These are not all the possible side effects of CRENESSITY. Call your healthcare provider for medical advice about side effects. You are encouraged to report negative side effects of prescription drugs to the FDA. Visit MedWatch at or call 1-800-FDA-1088. Dosage Forms and Strengths: CRENESSITY is available in 50 mg and 100 mg capsules and as an oral solution of 50 mg/mL. Please see full Prescribing Information. About Neurocrine Biosciences, Inc. Neurocrine Biosciences is a leading neuroscience-focused, biopharmaceutical company with a simple purpose: to relieve suffering for people with great needs, but few options. We are dedicated to discovering and developing life-changing treatments for patients with under-addressed neurological, neuroendocrine and neuropsychiatric disorders. The company's diverse portfolio includes FDA-approved treatments for tardive dyskinesia, chorea associated with Huntington's disease, classic congenital adrenal hyperplasia, endometriosis* and uterine fibroids,* as well as a robust pipeline including multiple compounds in mid- to late-phase clinical development across our core therapeutic areas. For three decades, we have applied our unique insight into neuroscience and the interconnections between brain and body systems to treat complex conditions. We relentlessly pursue medicines to ease the burden of debilitating diseases and disorders, because you deserve brave science. For more information, visit neurocrine.com, and follow the company on LinkedIn, X (formerly Twitter) and Facebook. (*in collaboration with AbbVie) The NEUROCRINE BIOSCIENCES Logo Lockup and YOU DESERVE BRAVE SCIENCE are registered trademarks of Neurocrine Biosciences, Inc. CRENESSITY and CAHtalyst are trademarks of Neurocrine Biosciences, Inc. Forward-Looking Statements In addition to historical facts, this press release contains forward-looking statements that involve a number of risks and uncertainties. These statements include, but are not limited to, statements regarding the potential benefits to be derived from CRENESSITY for the treatment of classic congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency; the value and benefits CRENESSITY brings to patients with CAH; the ability of Neurocrine Biosciences to ensure patients have access to CRENESSITY; and whether the results from our clinical trials of CRENESSITY are indicative of real-world results. Factors that could cause actual results to differ materially from those stated or implied in the forward-looking statements include, but are not limited to, the following: risks and uncertainties associated with Neurocrine Biosciences' business and finances in general, as well as risks and uncertainties associated with the commercialization of CRENESSITY; whether CRENESSITY receives adequate reimbursement from third-party payors; the degree and pace of market uptake of CRENESSITY; risks and uncertainties relating to competitive products and technological changes that may limit demand for CRENESSITY; risks associated with the Company's dependence on third parties for development and manufacturing activities related to CRENESSITY, and the ability of the Company to manage these third parties; risks that additional regulatory submissions for CRENESSITY or other product candidates may not occur or be submitted in a timely manner; risks that the FDA or other regulatory authorities may make adverse decisions regarding CRENESSITY; risks that post-approval CRENESSITY commitments or requirements may be delayed; risks that CRENESSITY may be precluded from commercialization by the proprietary or regulatory rights of third parties, or have unintended side effects, adverse reactions or incidents of misuse; risks and uncertainties relating to competitive products and technological changes that may limit demand for CRENESSITY; and other risks described in the Company's periodic reports filed with the Securities and Exchange Commission, including without limitation the Company's quarterly report on Form 10-Q for the quarter ended September 30, 2024. Neurocrine Biosciences disclaims any obligation to update the statements contained in this press release after the date hereof other than required by law. © 2024 Neurocrine Biosciences, Inc. All Rights Reserved. CP-CFT-US-0294 12/2024 SOURCE Neurocrine Biosciences, Inc. WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

A rare, inherited endocrine disorder whose standard treatments are steroids that introduce a wide range of side effects now has a new FDA-approved therapy, a non-steroidal Neurocrine Biosciences drug that could give the company another blockbuster seller. The FDA late Friday handed out two approvals for the Neurocrine drug crinecerfont as a treatment for classic congenital adrenal hyperplasia (CAH), a disease that leads to a hormone imbalance that can become fatal. A pill formulation of the San Diego-based biotech’s drug was approved for adults. An oral solution was approved for children age 4 and older. Both formulations will be marketed under the brand name Crenessity. The company claims it’s the first new CAH treatment in 70 years. CAH is an inherited disorder that affects the ability of adrenal glands to produce cortisol, a glucocorticoid hormone that plays a role in tissues and organs throughout the body. Low cortisol levels lead to increased secretion of two other hormones, adrenocorticotropic hormone (ACTH) and androgens. Without treatment, CAH leads to salt wasting (low levels of sodium that affect the brain and kidneys) and dehydration. Extremely low blood levels of cortisol can lead to adrenal crisis, a life-threatening complication. presented by Market Trends to Watch for Health Systems and Their Specialty Pharmacies The future looks bright for the integrated specialty pharmacy model – for health systems, providers, and most importantly, for patients. By Jake Gaffey, MBA, Chief Strategy Officer at Shields Health Solutions Standard CAH treatment includes synthetic versions of glucocorticoids intended to make up for deficient cortisol. But patients need higher doses than what is normally produced by the body to lower levels of ACTH and adrenal androgens. These supraphysiologic doses bring a wide range of complications associated with steroids, including weight gain, diabetes, cardiovascular disease, and osteoporosis. High GC doses can also have psychological and cognitive impacts. Crenessity is an oral small molecule designed to block the corticotropin-releasing factor type 1 receptor. Doing so inhibits secretion of ACTH from the pituitary gland, which in turn reduces production of adrenal androgens. FDA approval of Crenessity is based on results of a global Phase 3 study in adults and children that showed the drug led to significant glucocorticoid reductions compared to placebo after 24 weeks of treatment. The most common adverse reactions reported in the study included fatigue, headache, dizziness, and muscle and joint pain. Neurocrine said these side effects were temporary and mild to moderate in severity. The FDA approval covers the use of Crenessity as an adjunct to glucocorticoid replacement. For adults, the drug is twice daily pill. For children age 4 and older, dosing of the oral solution is according to patient weight. In a note sent to investors Monday, William Blair analyst Myles Minter said the drug’s label is nonrestrictive, permitting treatment of a broad range of CAH patients whether or not clinicians adjust dosing of glucocorticosteroids in patients receiving the two therapies together. Neurocrine said it would disclose Crenessity’s price when the product becomes available later this week. William Blair projects Crenessity will carry a $1,116 per dose price, which works out to about $264,784 per year —falling within the price range of orphan disease drugs. The new Neurocrine drug could achieve about $150 million in 2025 revenue, the firm projects. Peak global sales could reach $1.47 billion depending on regulatory approvals in other markets. Consumer / Employer Health Executives on Digital Transformation in Healthcare Hear executives from Quantum Health, Surescripts, EY, Clinical Architecture and Personify Health share their views on digital transformation in healthcare. By MedCity News “We see significant potential in the CAH market but acknowledge that for this to be a blockbuster $1 billion-plus commercial opportunity, there will need to be both patient and clinician education that supraphysiological glucocorticoid dosing would no longer be the only way to control androgen levels and prevent adrenal crises,” Minter wrote. “With this in mind, we view education activities and partnering with patient advocacy groups like the CARES Foundation as prudent steps ahead of the launch.” Neurocine expanded in endocrine disorders with the 2022 acquisition of Diurnal Group, a Wales-based company whose commercialized products include CAH drug Efmody, a hydrocortisone drug approved for treating CAH in adults and adolescents. At the time of the deal, Crenessity had reached Phase 3 testing. Neurocrine described the Diurnal acquisition as a way to add clinical development and commercial infrastructure in the U.K. The main revenue driver for Neurocrine is Ingrezza, which in 2017 became the first FDA-approved drug for the chronic movement disorder tardive dyskinesia. In the first nine months of 2024, the company reported $1.69 billion in Ingrezza sales, a 27% increase compared to the same period in the prior year. That drug alone accounts for 99% of Neurocrine product revenue, according to the company’s financial reports. FDA approval of Crenessity comes with a priority review voucher that Neurocrine may apply toward speedier regulatory review of a future rare disease drug. But most companies awarded these vouchers sell them to big pharmaceutical companies. Acadia Pharmaceuticals and PTC Therapeutics both received vouchers along with the recent FDA approvals of their respective rare disease drugs. Each voucher sold for $150 million. Illustration: QAI Publishing/Universal Images Group, via Getty Images